Garlic (Allium sativum) feeding impairs Sertoli cell junctional proteins in male Wistar rat testis: microscopy study.

Sertoli cell junctions, such as adhesion junction (AJ), gap junction (GJ) and tight junction (TJ), are important for maintaining spermatogenesis. In previous studies, we showed the inhibitory effect of crude garlic (Allium sativum, As) on spermatogenesis and steroidogenesis. The aim of this work was to complete our investigation on the impact of this plant, especially on Sertoli cell junctional proteins (SCJPs). During 1 month, 24 male rats were divided into groups: group control (0% of As) and treated groups fed 5%, 10% and 15% of As. Light and electron microscopy observations were performed to localise junctional proteins: connexin-43, Zona Occluding-1 and N-cadherin (immunohistochemistry) and to describe junctions. We showed that the specific cells involved in the localisation of the SCJP were similar in both control and treated groups, but with different immunoreactivity intensity between them. The electron microscopy observation focused on TJs between Sertoli cells, constituting the blood-testis barrier, showed ultrastructural changes such as fragmentation of TJs between adjacent Sertoli cell membranes and dilatation of rough endoplasmic reticulum saccules giving an aspect of scale to these junctions. We concluded that crude garlic consumption during 1 month induces perturbations on Sertoli cell junctions. These alterations can explain apoptosis in testicular germ cells previously showed.

The effect of methylation on some biological parameters in Salmonella enterica serovar Typhimurium.

Cell growth is tightly coupled to DNA replication and its methylation [Proc Natl Acad Sci U S A 93 (1996) 12206-12211]. In a culture medium, growing of Salmonella Typhimurium (S. Typhimurium) mutant cells (dam⁻) decreased (2.5 fold) relative to the wild type strain (dam⁺). In this study, we show that the reason for this growth deficiency is due to the DNA methylation. The absence of a Dam methyltransferase protein results in poor growth efficiency and disturbs the synchrony of replication initiation in vivo, as evaluated by flow cytometry. On the other hand, we show that lack of methylation could increase the DNA response to thermal stress (decreasing the DNA melting temperature, T(m)), and the reason for this effect is due to the methylation status and not to the number of guanine and cytosine bases (G+C) in the duplex DNA. Our results show that methylation is an epigenetic factor that may play a key role in the cell growth, the synchrony of DNA replication [C R Biologies 330 (2007) 576-580] and the stress protection.

[Sarcomatoid carcinomas of the upper airways]. / Carcinomes sarcomatoïdes des voies aéro-digestives supérieures.

INTRODUCTION: The sarcomatoid carcinoma of the superior aerodigestive tracts is a rare malignant tumour which presents diagnostic and therapeutic challenges. MATERIAL AND METHOD: We report 11 cases of spindle cell carcinomas of the upper airways. RESULTS: Sex-ratio was 10:1 and the mean age was 57.3 years (30 - 75 years). Nine patients were smokers and 4 presented with a history of radiation exposure. Tumoral locations were as follows: larynx: 6, hypopharynx: 1, oropharynx: 1, nasopharynx: 1, oral cavity: 2. Histological diagnosis in 3 cases required the use of immunohistochemical studies. Four patients were first seen at an advanced stage. This left 9 patients and among them 7 received a curative treatment: 5 by surgery alone, 1 by surgery and radiotherapy, 1 by radiotherapy, 1 by chemo-radiotherapy for the nasopharyngeal lesion and 1 by chemotherapy alone. Two patients died from their disease before treatment. With an average delay of 15.4 months, the rates of global survival and disease-free were 5/9 and 4/9 respectively. CONCLUSION: The sarcomatoid carcinoma of the upper airways is rare, but not unusual. Its diagnosis benefits from progresses in immunohistochemistry, but also from advances in the field of molecular biology. Its treatment and natural evolution remain controversial.

[Thyroid carcinoma and Hashimoto thyroiditis]. / Carcinome de la thyroïde et thyroïdite de Hashimoto.

OBJECTIVES: To study of the association between thyroid carcinoma and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: [corrected] Retrospective study of 78 patients undergoing surgery between 2001 and 2002, with a pathological diagnosis of Hashimoto's thyroiditis. The clinical data and complementary tests performed before surgery are reported. RESULTS: The mean age was 44.6 years, with 77 females and only one male. There were 12 cases of thyroid cancer associated with HT, mostly with the nodular form, with 11 papillary carcinoma (14.1%) and one non-hodgkin B lymphoma of the thyroid. Tumor size varied from 4 to 60 mm with a mean of 26 mm. There was one microcancer (size<10 mm). CONCLUSIONS: We did not find an increased incidence of thyroid cancer associated with this highly selected population of HT patients.

Chronic iodine overload and apoptosis in cold nodules from endemic multinodular goiters.

As apoptosis and necrosis are known to exist during experimental goiter development and involution, we studied them in ten Tunisian multinodular endemic goiters, five of them having received a chronic excess of iodine during six months. Apoptotic thyrocyte nuclei have been counted on hematoxylin-eosin stained semi-thin sections. Using immunoperoxidase on paraffin sections, bcl-2 and bax immunoreactivities have been evidenced, and CD34 positive microvessels counted; ultra-thin sections have also been observed. After six months of iodine overload, apoptotic thyrocytes were ten times more numerous; CD34 positive endothelial cells were diminished by one half bcl-2 immunoreactivity disappeared in thyrocytes and a bax one appeared in thyroid follicular and endothelial cells. Presence of numerous apoptotic follicular and endothelial cells was confirmed using electron microscopy. Chronic iodine excess induces apoptosis and necrosis of thyroid follicular and endothelial cells, leading to thyroglobulin accumulation in connective tissue.

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue.

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.

[Secondary head and neck osteosarcoma following treatment of undifferentiated nasopharyngeal neoplasms (UCNT)]. / Ostéosarcome secondaire de la tête et du cou après traitement de carcinome indifférencié du nasopharynx (UCNT).

Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage previously described most frequently after breast cancer and Hodgkin disease treatment with radio and/or chemotherapy. We report two cases of classical osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive loco-regional irradiation in the second case.

[Secondary mandibular fibrosarcoma after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma. Report of a case and review of the literature]. / Fibrosarcome secondaire de la mandibule après chimioradiothérapie pour carcinome indifférencié du nasopharynx. A propos d'une observation et revue de la littérature.

Secondary tumours to radio- and/or chemotherapy have rarely been reported after treatment for head and neck cancers. We report a case of mandibular fibrosarcoma observed 7 years after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma in a patient treated when 20 years old.

[Primary sino-nasal lymphomas. Apropos of 25 cases]. / Lymphomes primitifs nasosinusiens. A propos de 25 cas.

PURPOSE: To report on the epidemiological and therapeutic features of a series of Tunisian patients treated for primitive sinonasal lymphoma. PATIENTS AND METHODS: Our retrospective study concerns patients with histologically proven primitive sinonasal lymphoma diagnosed and treated at our institution from 1975 to 1997. Initial work-up included: clinical plus ENT examination, WBC, ESR, LDH, abdominal ultrasonography, bone marrow biopsy and facial CT-scan taken since 1985. All slides are reviewed and reclassified using the Kiel system. Treatment is based on radiotherapy with or without chemotherapy (mainly with the CHOP protocol). RESULTS: We collected 25 patients (22 males and three females, sex-ratio = 7) with a mean age of 48 years (18 to 78). Mean delay of consultation is 4 months and patients consulted mainly for nasal obstruction (65%), more rarely epistaxis (40%) or rhinorrhea. ENT examination showed a fungating nasal fossa tumor in 20% of cases, predominantly unilateral (80%), associated to cervical nodes in 25% of cases. High-grade lymphomas represented 60% of the cases, and 60% of the patients were stage IE. All stage IEs have been treated by exclusive radiotherapy while more advanced stages received combined chemo- and radiotherapy (eight patients). The five-year actuarial survival rate was 69% for the whole population, with a better prognosis for localized stage and low-grade lymphomas. DISCUSSION: Radiotherapy remains a standard treatment for sinonasal lymphomas, permitting us to cure localized stages. In extended stages (more than IE), combined chemoradiotherapy seems to be a good option, especially in case of bulky tumors as observed for the other nodal and extra-nodal head and neck lymphomas.

[Regional failure of hypopharyngeal squamous cell carcinoma]. / Echecs ganglionnaires du carcinome épidermoïde de l'hypopharynx.

PURPOSE: Lymph nodes and distant metastases contribute to the poor prognosis of hypopharyngeal squamous cell carcinoma. The purpose of this study is to estimate the frequency, mode and prognosis factors related to regional and distant metastasis. PATIENTS AND METHOD: The authors' report is based on a retrospective study concerning 271 hypopharyngeal squamous cell carcinoma, compiled in the service of Surgery of Head and Neck Cancers of the Salah-Azaïz Institute (1977-2002). Frequency and histoclinical characters of cervical and distant metastases have been assessed, as well as their prognosis factors among 155 patients treated in a curative purpose. RESULTS: 39.1% of the tumours were classified N0, 24.4% N1, 10.7% N2 and 25.8% N3 (UICC 2002). The cervical nodal invasion was significantly more frequent for the classified tumors T3T4 than for the T1T2 (for pyriform sinus, postcricoid esophagus, posterior wall, and total hypopharynx, respectively : P =0.001, P =0.007, P =0.047 and P =0.0005). A cervical lymphatic evidement was preferred in thirty two patients. Among N0, 46.9% were N+; The frequencies of the capsular effraction were not significantly different for the N0N1 from for the N2N3 (P =0.11). The two and five years survival rates were respectively 32.5 and 20.5% for N0, and 10.9% and zero for N3. The survival differences after two and five years between the N0N1 and the N2N3 were significant (P =0.04). A regional failure was noticed for 18.5% of the patients. The tumoral site did not influence significantly the rate of nodal failure (P =0.98), neither the clinical status N (P =0.34). Capsular effraction was a significant factor for the regional failure (P =0.007). Distant metastasis significantly occurred more frequently among the patients initially classified N2N3 than those classified N0N1 (P =0.03), and in case of capsular effraction (P =0.0009). CONCLUSION: Hypopharyngeal squamous cell carcinoma has a high rate of lymph nodes metastasis, correlated to the local extension, and a high rate of occult nodal metastasis. Lymph node clinical status does not seem to have influenced the patients survival; however, capsular effraction constitutes a major prognosis factor of regional failure and distant metastasis. Distant metastases are frequent, particularly in case of wide local and regional tumoral extension.

[Hypopharyngeal squamous cell carcinoma: retrospective study of 149 patients]. / Carcinome épidermoïde de l'hypopharynx: étude rétrospective de 149 traitements à visée curative.

PURPOSE: Hypopharyngeal squamous cell carcinoma is associated to one of the most unfavorable prognosis among the cancers of the head and neck. The purpose of this study is to analyze its therapeutic modalities in the Salah-Azaïz Institute (Tunis) and to compare their results. PATIENTS AND METHOD: This retrospective study concerns 271 hypopharyngeal squamous cell carcinomas, compiled in the Carcinologic Surgery Department of Head and Neck of the Salah-Azaïz Institute over a period of 25 years (from 1977 to 2002). The average age of the patients was of 56 years; sex-ratio was on average of 1.2 (man/woman). The indication of a curative treatment was initially retained for 149 (55%) patients, who were the only ones retained for the analysis of results. RESULTS: We retained the indication of a protocol including surgery and postoperating radiotherapy for 26.2% of the patients. Postoperation mortality rate was 5.1%; the operating rate of morbidity was 46.2%. For 13.5% of the patients, postoperating radiotherapy was permanently interrupted because of a gradual deterioration of the patients' health in the course of treatment. We retained the indication of exclusive radiotherapy for 59.7% of the patients. The average age was of 56 years and the sex-ratio of 1.2. The external radiotherapy was conventional. Radiotherapy had to be permanently interrupted in progress in 32.6% of cases on account of an deterioration of the patients' health; the rate of morbidity of the radiotherapy was 33.3%. We indicated a protocol of conservation of organ with induction chemotherapy for 21 patients (14.1%). The average age was of 53 years (28-65 years) and sex-ratio (man/woman) of 0.5. The global survival was 25.5% at one year, 18.1% at two years, 11.4% at three years and 7.4% at five years. All the patients selected for chemotherapy died in the course of treatment. The rates of survival in two and five years according to protocols surgery-radiotherapy and exclusive radiotherapy were respectively: 21.5 and 12%, and 18.3 and 10%. The difference between the rates of survival of this two protocols is not significant (P =0.08). CONCLUSION: Although the induction chemotherapy entails a particularly high death rate in our series, the association surgery-radiotherapy and the exclusive radiotherapy seem to be similarly efficient for the treatment of the hypopharyngeal carcinoma.

[Therapeutic results of 5-fluorouracil in multiple and unresectable facial carcinoma secondary to xeroderma pigmentosum]. / Résultats thérapeutiques du 5-fluorouracile dans les carcinomes multiples ou non resécables de la face secondaires au xeroderma pigmentosum (XP).

A prospective study was done to test the efficacy of 5-fluorouracil (topical and systemic) in multiple and unresectable histologically proven facial squamous cell carcinomas (SCC) secondary to XP. Twelve patients (7M/5F, mean age 19.8 years) with multiple facial SCC were treated between 1994 and 1997. 5-FU was used as a twice-a-day local application in the documented areas, by continuous infusion associated with cisplatin (2 patients) and short infusion combined with folic acid (3 patients). Evaluation was done by clinical examination every two months for topical therapy and after every cycle for systemic treatment. Median treatment duration was 12 months (2 to 36 months). Treatment was well tolerated excluding episodes of pruritus in the treated areas. We observed mainly superficial tumour regression followed by dryness and crusting. In 5 cases, we performed biopsies after treatment showing in one case an extensive fibrosis with absence of tumour. However in the remaining 4 cases, despite a superficial reduction of tumour and a reconstitution of the epidermis, viable and unmodified squamous cell carcinoma remained in the deeper dermis. In the 5 patients treated by systemic 5-FU, we observed 1 complete response and 3 partial responses. Despite a dissociation between a good cosmetic result and a relatively superficial effect, topical 5-FU represents a useful therapeutic option in multiple unresectable facial SCC in patients with XP. Systemic chemotherapy is recommended in the event of more extended or profound lesions.

[Dermatomyositis and nasopharyngeal carcinoma: 3 cases]. / Dermatomyosite et cancer du cavum : 3 observations.

BACKGROUND: Nasopharyngeal carcinoma is a common cancer in Tunisia with an estimated incidence of 1.8/100,000. The tumor shows a characteristic association with paraneoplastic syndromes. CASE REPORTS: We report three cases of histologically proven dermatomyositis associated with nasopharyngeal carcinoma in patients aged 40, 24 and 65 years. In all cases, the course of the paraneoplastic syndrome ran parallel to the nasopharyngeal carcinoma. DISCUSSION: Dermatomyositis is one of the numerous paraneoplastic syndromes associated with nasopharyngeal carcinoma. Systematic examination of the nasopharynx is required in case of dermatomyositis.

[Cervical lymph node involvement in carcinomas of the mobile tongue in Tunisia. Retrospective study of 135 cases]. / Envahissement ganglionnaire dans les carcinomes épidermoïdes de la langue mobile (CELM) en Tunisie.

OBJECTIVE: To report the profile of histologic cervical nodes involvement associated with mobile tongue squamous cell carcinoma. PATIENTS AND METHODS: Our retrospective study concerned patients treated from 1978 to 1998 by cervical neck dissection for mobile tongue carcinoma. RESULTS: A population of 135 patients (90 M/45 F, sex-ratio 2) with a 53.5 mean age (19 to 75) is analyzed. Clinical palpable nodes were present in 68 cases (50%) mainly submental-submaxillar (54). Histologic examination showed a node involvement in 54 cases without (32 cases) or with capsular rupture (22 cases) mainly in the jugulo-carotidian chain (46/54). Among the 67 clinically N0 patients collected after 1990, 22 patients (33%) exhibited an histological involvement vs 32/68 (47%) for the group presenting palpable cervical nodes for the whole period. Histologic node involvement seemed to be linked to the clinical status, node size and TNM stage. CONCLUSION: Cervical lymph node treatment needs to be systematic in mobile tongue carcinoma. The probability of histologic involvement is linked to the loco-regional extent of disease and influences the prognosis. In N0 patients, neck dissection is required because of the frequency of histological involvement, particularly when loss to follow-up may be expected.

[Mucous malignant melanoma of the neck and face. Experience at the Salah Azaiz Institute (Tunis)]. / Mélanomes malins muqueux cervico-faciaux. Expérience de l'Institut Salah Azaiz (Tunis).

The mucosal melanoma of the head and neck is rare and of late diagnosis. This retrospective study concerns 17 cases brought together in 30 years. Sex-ratio was of 1.1, the average age of 58 years. Tumoral seats were the following ones: nasal cavity and paranasal sinus (n = 10), nasopharyngeal cavity (n = 2), gingival seat (n = 2), palate (n = 1), laryngeal seat (n = 1), middle ear (n = 1). Tumoral extension was classified an follows: stage I: 52.9%, stage II: 17.6%, stage III: 29.4%. Melanomas were achromic in 23.5% of cases. On the therapeutic plan, 47.1% of the patients were treated in a purpose palliative because of the importance of the tumoral extension. Seven patients (41.2%) were treated surgically; three among them received an additional radiotherapy for an insufficient tumoral excision or adenopathy in break capsular. Two patients (11.8%) were treated by exclusive radiotherapy. The rates of survival were 17.6% in 2 years, and 5.9% in 5 years. The average duration of survival was of 18.1 months. The causes of failure were essentially local and metastatic.

[Thyroid papillary microcarcinoma. Salah Azaiz Institute experience]. / Microcarcinomes papillaires de la thyroïde. Expérience de l'Institut Salah Azaiz.

The incidence of thyroid papillary microcarcinoma appears to be increasing and therapeutic modalities remain controversial. This retrospective study concerns 25 cases, from 1978 to 1999. The circumstances of diagnosis were: a cervicotomy for thyroid nodule (88% of cases), cervical node metastases (8%), and osseous metastases (4%). The sensitivity of ultrasounds was 22.2%, that of scintigraphy was 9.1% and that of extemporaneous histological examination was 18.2%. Multifocality was found in 16% of cases and bilaterality in 16.6%. Treatment modalities were guided by histological examination. Adjunctive radioiodine ablation was used for 20% of the patients. The treatment of the osseous metastases was completed with external irradiation. The average follow up was 4.8 years (4 months to 19 years), with a rate of survival without disease of 100%.

[Thyroid oncocytomas]. / Les oncocytomes thyroidiens.

OBJECTIVE: Thyroid oncocytomas are rare tumors. They put problems of differential diagnosis enter malignant and benign forms. The modalities of the surgical treatment are controversial, in form as benign as malignant. Their prognosis is also debated. MATERIAL AND METHOD: Our retrospective study concerns 111 thyroid oncocytomas, so 6.5% of thyroid operated in our centre between 1981 and 2001. The sex-ratio of the patients was 0.16 with an average age of 41 years (15 to 72 years). RESULTS: All the fixed nodules, those associated to a recurrential paralysis, to tangible nodes or/and to microcalcifications on the radiography of the neck was malignant. Histological extemporaneous exam was not decisive in 16% of cases, among which 33% showed themselves malignant in the definitive exam, which put in evidence 9 carcinomas (8%). We treated benign oncocytomas by a loboisthmectomy for the isolated nodules, and the subtotal or total thyroidectomy for multinodular glands. For oncocytic carcinomas, we realized a total thyroidectomy with ganglionic taking and histological extemporaneous exam, followed by evidment in case of invasion (2 patients). For the 5 patients having presented a residual fixation, we obtained a white cartography after radioactive iodine administration. For the benign oncocytoma, we did ot notice any recurrences with an average drop of 28 months (2 months to 7 years). For carcinoma, 8 patients on 9 presented an actuarial survival without disease with an average drop of 44 months (18 months to 8 years). CONCLUSION: The diagnosis of malignancy of thyroid oncocytomas can be strongly evoked on however fickle clinical and radiological criteria; it can be eliminated only after definitive anatomo-pathological exam.